Thomas Körber

Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI)

Background— Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony–stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man. Methods and Results— Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89±35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 &mgr;g/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, &bgr;-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17±2.93 MNCCD34+/&mgr;L at baseline and 64.55±37.11 MNCCD34+/&mgr;L on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29±0.22 and 0.99±0.32 mm versus 0.49±0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 &mgr;g · kg−1 · min−1), wall motion score index showed improvement from 1.66±0.23 to 1.41±0.21 (P<0.004 versus control) and to 1.35±0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24±0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41±0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55±5 mm (P<0.002 versus control), and ejection fraction to 54±8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control). Conclusions— G-CSF and mobilization of MNCCD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.

Intentional occlusion of the left subclavian artery during stent-graft implantation in the thoracic aorta: risk and relevance.

Purpose: To examine the clinical consequences and/or potential need for postinterventional transposition after stent-graft occlusion of the left subclavian artery (LSA). Methods: The records of 171 consecutive patients (128 men; mean age 60.2±13.2 years, range 20–83) undergoing elective stent-graft repair in the thoracic aorta were reviewed to identify intentional endograft coverage of the ostial LSA, as documented by transesophageal echocardiography and/or aortography. Patients were treated for subacute type B dissection, true aneurysm, pseudoaneurysm, or previously operated type A dissection with persistent false lumen flow in the descending aorta. Among the 171 cases, 22 (12.9%) patients were identified with stent-graft occlusion of the LSA. Results: A systolic blood pressure differential existed between the right (138.4±14.0 mmHg) and the left (101.8±21.0 mmHg; p<0.05) arms after occlusion of the LSA. No patient showed a malperfusion syndrome during postinterventional hospitalization. During a mean follow-up of 24.0±15.8 months, 15 (68.2%) patients remained completely asymptomatic, with no functional deficit or temperature differential between the arms, while 7 patients reported mild symptoms of a subclavian steal syndrome. However, no patient required any secondary surgical intervention. Conclusions: Stent-graft—induced occlusion of the ostial LSA was tolerated by all patients without chronic functional deficit. In the absence of stenotic vertebral and/or carotid arteries and with a documented intact vertebrobasilar system, prophylactic transposition of the LSA is not required prior to intentional stent-graft occlusion of the LSA.

Percutaneous Endovascular Repair of Aneurysm After Previous Coarctation Surgery

Background—Formation of aortic aneurysm late after surgical repair of coarctation carries a significant risk of rupture and lethal outcome, and repeat surgery is associated with a 14% in-hospital mortality rate and morbidity from paraplegia, injury to the central nervous system, or from bleeding. The potential of nonsurgical endovascular repair by the use of stent-grafts in lieu of repeat surgery for postcoarctation aneurysm is unknown. Methods and Results—The concept of postsurgical endovascular stent-graft placement was evaluated with respect to feasibility and safety in 6 consecutive patients with late aneurysm formation after coarctation repair. All patients had aneurysm formation late after patch aortoplasty; placement of an elephant trunk during surgical repair of secondary type I dissection preceded formation of a local aneurysm in 2 cases. Patient age was 49±12 years, ranging from 31 to 68 years. Transluminal placement of customized stent-grafts was successful, with no 30-day or 1-year intervention-related mortality or morbidity. Follow-up survey of 11 to 47 months revealed optimal reconstruction of the thoracic aorta; 1 patient died 11 months after endovascular repair from cancer. Conclusions—Nonsurgical aortic reconstruction of postsurgical thoracic aneurysms forming late after coarctation repair is safe and feasible; interventional stent-graft placement has the potential to avoid repeat surgery of postsurgical aortic aneurysm.

Cardiac manifestation of the hypereosinophilic syndrome: new insights

Cardiac manifestation is the major cause of morbidity in patients with hypereosinophilic syndrome (HES). Clinical features range from heart failure to arterial embolism, which are caused by thickening of the endocardium and mural left ventricular thrombosis. Modern magnetic resonance imaging and echocardiography are able to detect fibrosis, eosinophilic infiltrate and thrombi to stage the fibrotic evolution of the disease. Treatment of HES involves standard medication for heart failure, anticoagulant therapy, immunosuppressive therapy and potentially surgical resection. The outcome of HES depends on both the progression of endocardial fibrosis and associated complications and the 5-year mortality is estimated at 30%.

Akute Becken-Beinvenenthrombose bei Agenesie des renalen Segments der Vena cava inferior

: A 19-year-old, otherwise asymptomatic man presented to the hospital of orthopaedic surgery with acute severe pain like lumbago. Symptomatic treatment was performed after extensive orthopaedic diagnostic procedures. On the third day after admission he showed clinical signs of deep vein thrombosis with painful swelling and livid discoloration of both legs. Colour duplex ultrasound revealed complete thrombosis of the leg and pelvic veins bilaterally, but the cranial extent was not clear. Contrast-enhanced helical computer tomography of the abdomen and the pelvis confirmed deep pelvic vein thrombosis and showed extension into the inferior vena cava. Moreover, the study revealed the agenesis of the renal segment of the inferior vena cava with collateral flow through dilated lumbar veins to enlarged azygous and hemiazygous, through vertebral and paravertebral venous plexus. The renals were drained via dilated capsular veins. The agenesis of renal vena cava is a very rare anomaly causing acute thrombosis of the deep leg and pelvic veins. Other risk factors of thromboembolic disease were not found. The patient was treated successfully with systemic thrombolysis. Therefore we used ultra-high streptokinase infusion (9 million units over 6 hours). Colour duplex ultrasound revealed good flow into deep leg and pelvic veins after three cycle of lysis. Magnetic resonance angiography of the abdomen and pelvis was performed to evaluate the successful fibrinolysis with complete recanalisation of the pelvic veins and to demonstrate the venous anatomy. Permanent oral anticoagulation with phenprocoumon is indicated to decrease the high rate of recurrent thrombosis. Compression stockings were prescribed. To prevent thrombosis, additional risk factors like smoking, immobilization and unusual physical activity should be strictly avoided.

Short-term growth hormone treatment and microcirculation: effects in patients with chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and contributes significantly to the high long-term cardiovascular morbidity and mortality. The short-term cardiovascular effects of recombinant human growth hormone (rhGH) in CKD patients (stages III-V) and healthy controls (n=15 each) were explored in a single-center, non-randomized pilot study. Subjects were investigated before, after a 7 day treatment with rhGH, and after a 7 day wash-out period. Microcirculation was assessed by nailfold capillaroscopy and leg strain gauge plethysmography. Echocardiography was performed and serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) were determined. Before the start of rhGH therapy, mean post-ischemic maximum flow velocity of erythrocytes (V(RBC)) and leg blood flow (LBF) in CKD patients were significantly reduced to 68% and 75% of that seen in controls, whereas V(RBC) and LBF under resting conditions were comparable. Treatment with rhGH significantly increased V(RBC) and LBF under resting conditions. Whereas maximum post-ischemic V(RBC) was improved by rhGH in patients and controls, maximum post-ischemic LBF increased in controls only. This was paralleled by a non-significant reduction of total vascular resistance, and increased heart rate and cardiac index. In conclusion, CKD patients respond to short-term rhGH treatment with significantly improved capillary blood flow, whereas only minor effects on total peripheral resistance and cardiac output were noted.

Die klinische Bedeutung der Verwendung unterschiedlicher Rekordertechnologien für die Ergebnisse der Analyse der Herzfrequenzvariabilität aus dem Langzeit-EKG

Summary The accuracy of the RR interval data acquisition is an essential prerequisite for reliable analysis of heart rate variability (HRV). In previous laboratory investigations, in which computerized electrocardiograms were simultaneously sampled at identical heart rates using digital and analog tape recorders, the superiority of the digital recorders was clearly demonstrated. Conventional tape recordings exhibit technical variability which may produce false positive HRV results. However, the clinical significance of this type of variability is not known.¶   Aim of the study: To characterize the clinical relevance of technical RR variability related to the conventional tape recording process.¶   Methods: In 20 patients with cardiac disease and stable sinus rhythm, 24-hour Holter monitoring was performed by connecting each patient simultaneously to a conventional tape and a digital Holter recorder (Ela medical) via the same leads. Technical variability was defined as the difference between the HRV results obtained by the respective analog (A) and digital (D) recording methods.¶   Results: For the following HRV indices significant A-D differences were found: SDNNindex: 38.47ms (A) vs. 36.17ms, p=0.003; RMSSD: 25.04ms (A) vs. 21.09ms (D), p<0.001; pNN50: 3.70% (A) vs. 2.40% (D), p=0.006; Total power: 1200.20ms2 (A) vs. 1076.55ms2 (D), p=0.032; LF power: 287.35ms2 (A) vs. 243.80ms2 (D), p=0.035; HF power: 72.50ms2 (A) vs. 54.95ms2 (D); p=0.001, and the LF/HF ratio: 4.47 (A) vs. 5.33 (D), p=0.037. No significant differenes were found for the following indices: SDNN: 95.59ms (A) vs. 94.74ms (D), p=0.29; and SDANN: 85.52ms (A) vs. 85.08ms (D), p=0.68.¶   Conclusions: Under both experimental and clinical conditions, higher HRV values were found in the conventional (tape) recordings. However, the technical variability was small in comparison with the mean values of normal HRV indices and their standard deviation. Thus, differences due to different recorder technology may be neglected in clinical practice. Nevertheless, in scientific HRV trials, it seems wise to use digital Holter recorders.ZusammenfassungHintergrund: In Laboruntersuchungen wurde anhand eines computergenerierten, starrfrequenten EKG-Signals die Überlegenheit der digitalen gegenüber der analogen Aufzeichnungstechnologie in der zeitlichen Akquisitionsgenauigkeit der R-R-Intervalle, als rechnerischer Ausgangsgröße aller Verfahren der HRV-Analyse, belegt. Bandsystemen sind demnach Akquisitionsungenauigkeiten immanent, die eine technisch bedingte, höhere künstliche Variabilität erzeugen.¶   Zielstellung und Methodik: Da die Absolutwerte der künstlichen Variabilität im Vergleich zu den allgemein akzeptierten HRV- Normwerten jedoch vergleichsweise gering ausfallen, sollte die klinische Bedeutung der Ergebnisse aus dem Labor untersucht werden. Dazu wurden analoge Magnetband (A)- und digitale (D) Langzeit-EKG-Rekorder der Firma Ela medical unter Verwendung derselben Elektroden parallelgeschaltet und 24-Stunden-Registrierungen an Patienten mit einer Herzerkrankung und Sinusrhythmus vorgenommen. Unter gleichen Analyse- und Auswertebedingungen lassen sich dann Einflüsse unterschiedlicher Akquisitionsgenauigkeiten über die Differenz zwischen analoger und digitaler Aufzeichungstechnologie für Indizes der Zeit- und der Frequenzdomäne erfassen.¶   Ergebnisse: Die Analyse der Parallelregistrierungen an 20 Patienten ergab bei den gemittelten Werten statistisch signifikante positive Analog-Digital-Differenzen für die Indizes SDNN-Index (A: 38,47ms; D: 36,17ms; p=0,003), RMSSD (A: 25,04ms; D: 21,09ms; p <0,001), pNN50 (A: 3,70%; D: 2,40%; p=0,006), Total power (A: 1200,20ms2; D: 1076,55ms2; p=0,032), LF (A: 287,35ms2; D: 243,80ms2; p=0,035), HF (A: 72,50ms2; D: 54,95ms2; p=0,001) sowie signifikant negative A-D-Differenzen für die LF/HF ratio (A: 4,47; D: 5,33; p=0,037). Für SDNN (A: 95,59ms; D: 94,74ms; p=0,29) und SDANN (A: 85,52ms; D: 85,08ms; p=0,68) waren die Unterschiede nicht signifikant.¶   Schlussfolgerungen: Damit ist belegt, dass auch unter klinischen Bedingungen aus Bandregistrierungen künstlich höhere Variabilitäten bestimmt werden. Allerdings muss auch festgestellt werden, dass die Differenzen für die Indizes der Zeitdomäne zwischen Analog- und Digitalregistrierung eher geringer ausfallen als in den Laborversuchen mit computergeneriertem EKG und die Absolutwerte der Differenzen der HRV-Indizes in Relation zur Variationsbreite der Normwerte wenig bedeutsam sind. Somit hat die Wahl der Aufzeichnungstechnologie der Holter-EKG-Systeme für die Bestimmung der HRV im klinischen Alltag nur geringe Bedeutung. Bei der Durchführung von Studien und Betreuung von Hochrisikopatienten ist jedoch die Auswahl der Rekordertechnik kritisch zu überdenken und die digitale Aufzeichnungstechnologie grundsätzlich zu bevorzugen.

Behandlung des akuten ST-Hebungsinfarkts in Netzwerkstrukturen

ZusammenfassungDie erfolgreiche Therapie des akuten Myokardinfarkts (STEMI [ST-Hebungsinfarkt]) erfordert eine schnellstmögliche und komplette Revaskularisation, da die Prognose des Infarktpatienten vom Zeitintervall zwischen Gefäßverschluss und Wiedereröffnung mit resultierendem normalem Fluss der Infarktarterie abhängt. Die zeitgerechte primäre perkutane Koronarintervention (PPCI) durch ein erfahrenes Team ist selbst der prähospitalen Thrombolysetherapie überlegen und wurde von nationalen und internationalen Fachgesellschaften zur Therapie der ersten Wahl erklärt.Zur flächenhaften Durchsetzung der PPCI wird die Einrichtung von Netzwerken mit direktem Transport des Infarktpatienten in ein geeignetes Herzkatheterlabor, auch unter Umgehung eines näher gelegenen „nichtinvasiven“ Krankenhauses, empfohlen. Mittels Netzwerklogistik und eines standardisierten Therapiepfads können die prognostisch relevanten Therapiezeitintervalle eingehalten werden. Im PCI-Zentrum sind hierzu die Bereithaltung aller notwendigen logistischen, apparativen und personellen Voraussetzungen, insbesondere die ständige Bereitschaft eines erfahrenen interventionellen Teams, sowie eine einfache Patientenanmeldung via Hotline erforderlich.Im Drip&Ship-Netzwerk Rostock wurden innerhalb von 5 Jahren 1 022 Patienten mit STEMI interventionell behandelt, von denen 490 Patienten aus einem peripheren Krankenhaus transferiert und 532 Patienten direkt im PCI-Zentrum vorgestellt wurden. Exakt 95,1% aller transferierten und 94,8% aller direkt aufgenommenen Patienten wurden einer sofortigen PCI unterzogen, in deren Ergebnis ein normalisierter Koronarfluss in 96% beider Gruppen erzielt wurde. In der 12-Monats-Nachbeobachtung unterschieden sich die Patienten beider Gruppen weder hinsichtlich des Ausmaßes der Myokardnekrose noch bezüglich Mortalität, NYHA-Stadium und linksventrikulärer Ejektionsfraktion. Die effiziente PCI-Netzwerklogistik sichert somit den Patienten mit STEMI in ländlichen Regionen dieselbe Prognose wie bei innerstädtischer Versorgung.AbstractManagement of acute ST elevation myocardial infarction (STEMI) demands rapid and complete reperfusion of the infarct-related artery (IRA). With postinfarction prognosis depending on time delay from onset of symptoms to complete reperfusion (TIMI 3 flow) of the IRA, primary percutaneous coronary intervention (PPCI) performed by an experienced team has been shown to be superior to thrombolytic therapy with lower mortality, less frequent occurrence of nonfatal reinfarction and stroke, and thus represents the preferred treatment strategy according to the national and international guidelines.For regional implementation of PPCI, particularly in rural areas, information and transfer logistics within networks of care and direct transport of an infarction patient to a PCI hospital rather than to the closest hospital are a challenge. With successful implementation of network logistics and standardized therapeutic pathways, current guidelines and requested timelines versus thrombolysis could be met. The implemented logistics comprised 24 h/7 days stand-by services of an experienced PCI team, direct telephone hotline contact between rescue service/emergency physician and interventional cardiologist on call, and direct open access to a catheterization laboratory at any time.Within the Drip&Ship network Rostock, to date (July 2007) 1,022 consecutive patients with PCI for STEMI were documented and analyzed over 5 years; of these, 490 patients were transferred from a community hospital to the PCI center and 532 patients were admitted directly to the interventional center. In 95.1% of all transferred and in 94.8% of all directly admitted patients, PCI was successfully accomplished upon arrival. A normalized flow to the IRA after PCI was documented in 96% of both groups, no patient was subjected to thrombolytic therapy. At 12-month follow-up, there were no differences between both groups with respect to infarct size and mortality. Moreover, there was no evidence of differences in left ventricular ejection fraction between groups. Thus, transportation of STEMI patients within an established PCI network did not result in any prognostic disadvantage. Efficient network logistics with transportation for PPCI in acute STEMI ensure both safety and outcome profiles similar to patients treated by PCI in metropolitan areas.

Realisierbarkeit und Sicherheit einer alleinigen AAI(R)-Schrittmacherbehandlung beim isolierten symptomatischen Sinusknotensyndrom

SummaryRecent investigations prove that AAI(R) pacing is the “ideal” stimulation mode in isolated sick sinus syndrome. Nevertheless, in Germany this bradycardia is treated by AAI(R) pacemakers in less than 4% of cases compared to 25% in other countries. In our institution treatment of patients with isolated sick sinus syndrome is uniform and corresponds to the actual guidelines since the early 1990s; therefore the aim of our study was to analyze feasibility and safety of AAI(R) pacing in a retrospective study.Between 1998 and 2000, 52 of 165 patients (31.5%) with isolated sick sinus syndrome were treated by an AAI(R) pacemaker. The median follow-up duration was 51.5 months (minimal: 36 months). 6 patients died, in all cases unrelated to the stimulation mode. Three patients required reoperations, however, in only one case due to second degree AV block with the need for upgrading to DDD stimulation. Thus, the yearly incidence of this specific complication in the AAI(R) cohort is 0.64%.In conclusion, permanent atrial stimulation in isolated sick sinus syndrome is feasible in a quarter of all cases. It is safe if performed corresponding to actual guidelines. Additionally, single lead AAI(R) pacing is a cost-effective therapy and the only stimulation mode which, today, reliably prevents unnecessary right ventricular stimulation. If, on the other hand, algorithms providing automatic mode switching from AAI to DDD and vice versa are implemented reliably into all dual chamber pacemakers, single chamber atrial pacing will no longer be a subject for discussion.ZusammenfassungNeuere Erkenntnisse lassen den AAI(R)-Modus als „ideale“ Therapieform beim isolierten Sinusknotensyndrom erkennen. Dessen ungeachtet ist der Anteil permanenter AAI(R)-Schrittmacher bei dieser Bradykardie in Deutschland mit unter 4% noch gering, während er in anderen Ländern mehr als 25% erreicht. Da in unserer Einrichtung die Indikation zur AAI(R)-Stimulation beim Sinusknotensyndrom seit Anfang der 90er Jahre nach einheitlichen und bereits den aktuellen Leitlinien entsprechenden Kriterien gestellt wird, war es Ziel der Studie, anhand neuerer, retrospektiv ermittelter Zahlen zu Realisierbarkeit und Sicherheit dieser Therapieform Stellung zu nehmen.Im 3-Jahreszeitraum 1998–2000 wurden 165 Patienten wegen eines isolierten symptomatischen Sinusknotensyndroms mit einem Schrittmacher versorgt. Davon erhielten 52 (31,5%) Patienten einen permanenten AAI(R)-Schrittmacher. Sie wurden im Median 51,5 Monate, mindestens aber 36 Monate nachbeobachtet. 6 Patienten verstarben, ohne dass die Todesursache im Zusammenhang mit dem gewählten Schrittmacher-Modus stand. Reeingriffe waren bei 3 Patienten notwendig. Dabei handelte es sich nur bei einer Patientin um die Aufrüstung zum DDD-System wegen eines asymptomatischen AV-Blocks. Das entspricht einer Häufigkeit dieser spezifischen Komplikation von 0,64% pro Jahr.Somit kann davon ausgegangen werden, dass eine alleinige permanente Vorhofstimulation bei etwa einem Viertel der Fälle mit isoliertem Sinusknotensyndrom realisierbar und bei leitliniengerechtem Vorgehen auch ausreichend sicher ist. Damit können einerseits Kosten gespart werden. Zum anderen wird derzeit allein durch den AAI-Modus eine unnötige rechtsventrikuläre Stimulation vermieden. Noch offen ist die Frage, ob zukünftig zuverlässig arbeitende und in allen DDD(R)-Schrittmachern angebotene Algorithmen zum automatischen Modeswitch zwischen AAI und DDD die Diskussion um den Einkammer-AAI(R)-Schrittmacher überflüssig machen.

Perforiertes Mitralklappenaneurysma als seltene Verlaufsform einer bakteriellen Endokarditis

A 65 year old man with a history of mechanical aortic valve replacement acquired Enterococcus faecalis mediated infective endocarditis about 3 years later. Transesophageal echocardiography revealed formation of an aneurysm confined to the anterior mitral valve leaflet. The aortic valve revealed no signs of endocarditis by transesophageal ultrasound. With sudden perforation of the mitral valve aneurysm, subsequent hemodynamic deterioration and pulmonary oedema, the patient underwent emergency mitral and aortic valve replacement. The postoperative course was uneventful. Wir berichten über einen 65jährigen Patienten mit Zustand nach mechanischem Klappenersatz bei Aortenklappeninsuffizienz, der etwa 3Jahre nach Klappenersatzoperation an einer Endokarditis erkrankte. Als Erreger konnte Enterokokkus faecalis nachgewiesen werden. Die transösophageale Echokardiografie sicherte den seltenen Befund eines Aneurysmas des anterioren Mitralklappensegels. Die Aortenklappenprothese und die Aortenwurzel zeigten keine endokarditischen Veränderungen. Die plötzliche Perforation des Mitralklappenaneurysmas im Erkrankungsverlauf führte zur akuten hochgradigen Mitralinsuffizienz mit beatmungspflichtigem Lungenödem. Die erforderliche notfallmäßige Doppelklappenersatzoperation verlief ohne postoperative Komplikationen.